Because common epithelial cancers have resisted most therapeutic efforts, much hope is currently placed in chemoprevention (1). Chemopreventative measures are especially important in patients who are at elevated risk for neoplasia due to genetic or environmental factors. Though research on such agents is now blossoming, only a few compounds have been shown to be useful in vivo. Among these are nonsteroidal anti-inflammatory drugs (NSAID), which are effective in reducing colon tumors in genetically susceptible humans (2) and rodents (3,4). Additionally, epidemiological studies have determined that NSAID administration among the general population is associated with a reduced risk of colon cancer death (5).
Further progress in this area will in part depend on understanding the mechanisms by which such chemopreventative agents exert their protective effects. It is already well known that NSAID can inhibit cyclooxygenases (COX) (reviewed in 6), and some studies have shown that NSAID can induce apoptosis (also called programmed cell death or PCD) (7). Moreover, expression of COX-2 is elevated in colorectal tumors (8) and can protect intestinal epithelial cells from apoptosis (9). However, the biochemical mechanisms by which the NSAID and COX alter colonic cell proliferation have been largely unknown (reviewed in 10).
An understanding of the mechanisms by which known chemopreventative agents protect against tumors may lead to new methods of screening for other agents that are effective in preventing or treating cancers (cancer chemopreventative agents). There is a continuing need in the art for chemopreventative and chemotherapeutic agents.